9onh

Structure of ancestral-reconstructed cytochrome P450 11A1 (CYP11A1) in complex with desmosterol

spinqualitylabelsall models 9onh, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9onh is a 1 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Ligands: HEM, MHQ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The cytochrome P450 enzyme 11A1 (CYP11A1) is the most important player in steroid hormone biosynthesis, catalysing the first and rate-limiting step, the side-chain cleavage of cholesterol to pregnenolone, which provides the precursor for all major steroid hormones. A resurrected ancestral isoform of CYP11A (CYP11A_N1) exhibits different substrate specificities to extant vertebrate CYP11A1 forms which implies an evolutionary change in structural features. Hence, we solved the structure of the resurrected ancestral CYP11A_N1 isoform and identified the major structural changes between ancestral and extant CYP11A isoforms that lead to different catalytic properties for cholesterol metabolism. Our work presents the first structure of an ancestral mitochondrial cytochrome P450 and highlights how structural changes shaped the evolution of steroid hormone biosynthesis. How evolution shaped the structure of steroidogenic cytochrome P450 11A.,Chagas BCA, Brixius B, Wang PC, Pirhadi S, Aziz O, Koes DR, Gillam EMJ, Bernhardt R, Brixius-Anderko S J Inorg Biochem. 2025 Oct 9;274:113105. doi: 10.1016/j.jinorgbio.2025.113105. PMID:41075759 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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